Quinoline → 2-Chloro-5-(trifluoromethyl)nicotinonitrile

Participants

Reaction Steps

To a mixture of phosphorous oxychloride (13.4 mL, 144 mmol) and quinoline (8.7 mL, 73 mmol) was added the product from Step C above (24.6 g, 131 mmol) and the resultant mixture was heated to reflux for 3 h. The reaction was cooled to 100° C. before water (70 mL) was slowly added. The mixture was further cooled to room temperature and neutralized by the cautious addition of saturated aqueous sodium bicarbonate solution. The aqueous layer was extracted with three portions of ethyl acetate and the organic layers were combined, dried over magnesium sulfate and concentrated in vacuo. The crude product was purified by flash chromatography to afford the desired compound. 1H NMR (500 MHz, CDCl3) δ 8.88 (d, J=2.0 Hz, 1H), 8.26 (d, J=2.5 Hz, 1H).

Provenance & Evidence